Liposomal nanoparticle mediated gene modulation for the treatment of melanoma in murine models.

Abstract

Melanoma is a treatment-resistant and highly aggressive form of skin cancer. The aberrant activation of the Wnt/β-catenin pathway is a key driver of proliferation, tumor progression, and metastasis in many cancers, including melanoma. The active involvement in tumor growth and immune evasion makes the Wnt/β lipoplexes-catenin pathway a critical therapeutic target. Recent advancements in gene delivery systems, such as liposomal nanoparticles (LNPs), have opened new possibilities for targeted cancer therapies by efficiently delivering genetic material, including microRNA (miRNA), to cancer cells with minimal off-target effects. Among potential gene-based therapies, miR-124 has emerged as a promising candidate for targeting the Wnt/β-catenin pathway. However, a major challenge in miRNA-based therapeutics is the efficient delivery of miRNA to tumor cells. By using cationic liposomes to form lipoplexes with miR-124 plasmids, we aim to evaluate the efficiency of lipoplex-mediated delivery and transfection in both in vitro and in vivo melanoma models and observe their effects on WNT/β-catenin signaling and tumor growth. The application of lipoplexes in gene-based therapies represents a promising approach to improve treatment outcomes for melanoma patients.